Aseptic loosening continues to be a problem with total hip replacements. In cemented total hip replacement, mechanically induced loosening most often initiates at the stem-cement or cement-bone interface. Improving the outcomes of cemented total hip replacement is limited by our lack of understanding of the actual mechanical conditions that cause loosening, and the multifactorial nature of the failure process that depends on stem design, stem surface conditions, and cementing technique. In this work, a research program is described to investigate: (1) the specific mechanical fatigue conditions under which the stem-cement and cement-bone interfaces fail; (2) the manner in which stem design, stem surface, and cementing process contribute to the fatigue failure process at the interfaces and in the bulk cement; and (3) the interactions between these three design factors in affecting the fatigue failure process. The end goal of this research is to define design guidelines that will reduce the revision rates of cemented hip replacements due to implant loosening. It is the hypothesis of this work that stem design, stem surface, and cementing conditions can each effect the overall failure (loosening) of the implant system. In the proposed research, fracture mechanics-based approaches will be used to characterized the fatigue behavior and failure of the stem-cement and cement-bone interfaces. Models for interface response will be developed from a combination of experimental and theoretical methods, and these models will be verified by comparison of predicted to observed results for experiments that are different than those used for model development. Cyclic fatigue experiments of cemented stem construct will be performed with an aggressive stair climbing loading regime for each of the design conditions. These experiments will directly test the hypothesis stated above through use of a 23 factorial experimental design. Finally, fully 3-D fatigue models of each of the eight design cases will be performed to elucidate the failure mechanisms found in the experiments. When combined, the experimental and computational approaches will provide design guidelines that could significantly reduce revision rates of cemented hip replacements due to implant loosening.